The implementation of a screening program including conventional x-ray mammography and palpation has been effective for the detection of breast cancer in postmenopausal women. However, due to the Comparatively increased tissue cellularity in younger women as well as in other patients, the image quality of mammograms is compromised due to radiative scatter. In this application, the development of a novel, yet tested optical imaging technique which utilizes scattered light for image formation is proposed. This application seeks to adapt frequency-domain, fluorescence lifetime spectroscopy and imaging techniques to monitor photon migration characteristics for rapid detection and localization of breast lesions on the basis of optical properties. Essentially, the technology consists of illuminating a tissue with light whose intensity is sinusoidally modulated at MHz frequency, f. The light emitted at a distance p, is both phase- shifted by theta and demodulated by factor, M. Using frequency-domain imaging techniques developed at the Center for Fluorescence Spectroscopy at the University of Maryland, we have demonstrated that rapidly acquired theta and M "images" contain information for direct detection and localization of small optical heterogeneities obscured by tissue-like scattering. In these proposed preclinical studies, the development of photon migration imaging (PMI) technology is sought specifically for breast screening the target group of premenopausal women for whom x-ray mammography is not effective. The planned approach will be to first develop optical phantoms based upon measurement of the optical properties of human normal and lesion tissues collected from breast resection surgeries. Secondly, frequency domain PMI measurements will be conducted on these phantoms to discriminate the physiological range of optical property differences which must exist between the lesion and surrounding tissue for detection, localization, and characterization (i.e., whether the lesion is cystic or solid mass) via PMI measurements. Phantom studies will also be conducted to ascertain the minimal detectable size (MDS) of lesions and the x-y-z resolution obtained in x-y PMI measurements as a function of the optical property differences between the lesion and surrounding tissue, the modulation frequency employed, and the depth of the lesion. It is anticipated that the resulting studies will provide the foundation for future clinical trials of PMI breast screening in patients who are not candidates for conventional mammography.